Low-dose of thalidomide in the treatment of refractory myeloma

scientific correspondence
1111
reported 5 cases of PTCL, all with a long-lasting
history of granulomatosis, hepatosplenomegaly,
HBsAg and EBV-VCA positivity. The only surviving
patient had received an allogeneic bone-marrow
transplantation. Our two children had been
infected by EBV with a chronic high titer of IgG
against EBV-VCA, consistent with a life-long
infection. 9 EBV may infect T-cells creating reactive
lymphoid proliferations without contributing
to the neoplastic process; however EBV or other
viral infections (i.e. Cytomegalovirus, hepatitis
B), or immune defects suppressing NK activity –
such as altered T4/T8 ratio – may lead to neoplastic
transformation in particular hosts, and
this could be the case with our patients. All available
lymph node samples were therefore submitted
to EBV-DNA detection without finding
amplification of the viral genome. The presence
of EBV-DNA is a feature of angioimmunoblastic
PTCL found in Eastern Countries, being less
common in Europe. 3,10 As to optimal treatment,
we agree with the Taiwan group: 3 marrow transplantation
can cure this disease. The role of
retinoic acid cannot be assessed by anecdotal
experiences, even though malignant cell differentiation
and apoptosis might depend on
retinoic acid administration. 10 No national or
international co-operative group is currently
dealing with poor-prognosis PTCL: a common
study is therefore needed, perhaps including
both adults and children.
Maura Massimino, Daniela Perotti, Filippo Spreafico,
Roberto Luksch, Alberto Garaventa,° Roberto Giardini
Istituto Nazionale Tumori, Milan; °Istituto G. Gaslini, Genoa, Italy
Funding
This work was partially supported by Associazione
Bianca Garavaglia, Busto Arsizio (VA) and AIRC.
Key words
Childhood non-Hodgkin’s lymphoma, PTCL, ALCL.
Correspondence
Maura Massimino, M.D., Division of Pediatric
Oncology, Istituto Nazionale Tumori, via G. Venezian,
1, 20133 Milan, Italy. Phone: international +39-02-
2390593 – Fax: international +39-02-2665642 –
E-mail: massimino@istitutotumori.mi.it
References
1. Harris NL, Jaffe ES, Stein H, et al. A revised European-
American classification of lymphoid neoplasms: a proposal
from the International Lymphoma Study Group.
Blood 1994; 84:1361-92
2. Jaffe ES, Harris NL, Diebold J, et al. World Health
Organization classification of neoplastic diseases of
the hematopoietic and lymphoid tissues. A progress
report. Am J Clin Pathol 1999, 111, S8-12.
3. Lin KH, Su IJ, Chen RL, et al. Peripheral T-cell lymphoma
in childhood: a report of five cases in Taiwan.
Med Pediatr Oncol 1994; 23:26-32.
4. Agnarsson BA, Kadin ME. Peripheral T-cell lymphomas
in children. Sem Diagn Pathol 1995; 12:314-
24.
5. Neuhauser TS, Lancaster K, Haws R, et al. Rapidly
progressive T cell lymphoma presenting as acute renal
failure: case report and review of the literature. Pediatr
Pathol Lab Med 1997; 17:449-60.
6. de Terlizzi M, Toma MG, Santostasi T, et al. Angioimmunoblastic
lymphadenopathy with dysproteinemia:
report of a case in infancy with review of literature.
Pediatr Hematol Oncol 1989; 6:37-44.
7. Leake J, Kellie SJ, Pritchard J, et al. Peripheral T-cell
lymphoma in childhood. A clinicopathologic study of
six cases. Histopathology 1989; 14:225-8.
8. Cheng AL, Su IJ, Chen CC, et al. Characteristic clinico-pathologic
feature of Epstein-Barr virus associated
peripheral T-cell lymphoma. Cancer 1993; 72:909-16.
9. Jones JF, Shurin S, Abramowsky C, et al. T-cell lymphomas
containing Epstein-Barr viral DNA in patients
with chronic Epstein-Barr virus infections. N Engl J
Med 1988; 318:733-41.
10. Cheng AL, Su IJ, Chen CC, et al. Use of retinoic acids
in the treatment of peripheral T-cell lymphoma: a pilot
study. J Clin Oncol 1994; 12:1185-92.
Low-dose thalidomide in the treatment of
refractory myeloma
In this report we present five cases of refractory
multiple myeloma successfully treated
with low doses of thalidomide.
Sir,
Barlogie’s group recently reported the results
of a phase 2 study with thalidomide, as a single
agent, in the treatment of refractory myeloma. 1
In this study the rate of response was 32%, as
shown by a reduction of at least 25% of the M-
component. The study considered a gradual
increase in the dose of thalidomide up to a maximum
daily dose of 800 mg. The toxicity linked
to the treatment was not negligible. Furthermore,
in the last six months several preliminary
reports have shown the efficacy of low dose
thalidomide in the treatment of resistant myeloma.
2-8 We present our experience on a small
group of patients with refractory myeloma treated
with low dose thalidomide. The study included
five patients (4 males, 1 female; median age
67 years, range 58-76). All patients had received
two or more different regimens of conventional
therapy. No patient had been submitted to high
dose chemotherapy with autologous hematopoietic
stem cell transplantation. At the start of
thalidomide therapy all patients had progressive
disease. The patients started with 200 mg/day
of thalidomide as a single therapeutic agent
after providing written consent. The dose has
not been increased during the whole period of
the treatment. In our patients the side effects
were mild or moderate (grade 1 or 2 according
Haematologica vol. 85(10):October 2000

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scientific correspondence
Table 1.
Patient #1 Patient #2 Patient #3
S maxR % S maxR % S maxR %
Paraprotein levels (g/dL)
6 0.8 87 3 0.3 90 3.3 1.6 51.5
Bone marrow plasmacytosis (%)
60 11 82 82 30 63 30 10 66
β2-microglobulin (mg/L)
10.4 3.2 69 8 4.9 39 3.82 1.73 55
S= starting value; MaxR= the best response; %= percentage of response.
to WHO criteria). The dose of thalidomide was
reduced to 100 mg/day in 2 patients because of
constipation and a transient reduction of
platelets. The median time of treatment has
been 5 months (range 2-9). Four of five patients
(80%) have responded to the therapy – two
patients with more than 70% reduction of the
M-component levels, one with more than 50%
and the last one with about a 30% reduction.
The fifth patient had no response and stopped
the therapy after two months. The interval of
time necessary to obtain the best rate of
response to the therapy was 50 days (range 34-
64). In the three patients with the best response
to the therapy a reduction in the percentage of
plasma cells in bone marrow, β2 microglobulin
levels and C reactive protein was evident (Table
1). Furthermore, a good response was obtained
in one patient who reduced the dose of
thalidomide to 100 mg/die early in treatment. In
conclusion, although our experience concerns
only five cases, we confirm the results published
in scientific literature 1-8 on the efficacy of
thalidomide in myeloma therapy. We point out
the possibility of obtaining a good objective
response 9 with lower and better tolerated dose
of drug. We, therefore, think it would be desirable
to study the most suitable dose of thalidomide
in a larger number of patients.
Massimo Pini, Anna Baraldi, Daniela Pietrasanta,
Bernardino Allione, Lorella Depaoli, Flavia Salvi, Alessandro Levis
Hematology Division, Azienda Ospedaliera SS. Antonio e Biagio,
Alessandria, Italy
Key words
Multiple myeloma, low dose thalidomide, side effects.
Correspondence
Massimo Pini M.D., Hematology Division, Az.
Ospedaliera SS. Antonio e Biagio C. Arrigo, via Venezia
16, 15100 Alessandria, Italy. Phone: international
+39-0131-206809 – Fax: international +39-0131-
261029 – E-mail: alevis@ospedale.al.it
References
1. Singhal S, Metha J, Desikan R, et al. Antitumor activity
of thalidomide in refractory multiple myeloma. N
Engl J Med 1999; 341:1565-71.
2. Barlogie B, Desikan R, Munshi N, et al. Single course
D.T. PACE antiangiochemotherapy effects CR in plasma
cells leukemia and fulminant multiple myeloma
(MM). Blood 1998; Suppl 1: 273b.
3. Kneller A, Raanani P, Hardan I, et al. Therapy with
thalidomide in refractory multiple myeloma patients –
the revival of an old drug. Br J Haematol 2000; 108:
391-3.
4. Durie BGM, Stephan DE. Efficacy of low dose thalidomide
(T) in multiple myeloma. Blood 1999; Suppl
1413.
5. Chen CI, Adesanya A, Sutton DM, et al. Low-dose
Thalidomide in patients with advanced, refractory
multiple myeloma. Blood 1999; Suppl: 4603 abstract.
6. Sabir T, Raza S, Anderson L, et al. Thalidomide is
effective in the treatment of recurrent, refractory multiple
myeloma (MM). Blood 1999; Suppl 548.
7. Zomas A, Anagnostopoulos N, Dimopoulos MA. Successful
treatment of multiple myeloma relapsing after
high-dose therapy and autologous transplantation
with thalidomide as single agent. Bone Marrow Transplant
2000; 25:1319-20.
8. Juliusson G, Celsing F, Turesson I, Lenhoff S, Adriansson
M, Malm C. Frequent good partial remissions
from thalidomide including best response ever in
patients with advanced refractory and relapsed myeloma.
Br J Haematol 2000; 109:89-96.
9. San Miguel JF, Blade Creixenti J, Garcia-Sanz R. Treatment
of multiple myeloma. Haematologica 1999; 84:
36-58.
Feasibility and efficacy of high-dose etoposide
followed by low-dose granulocyte colony-stimulating
factor as a mobilization regimen in
patients with non-Hodgkin’s lymphoma
The administration of high-dose (HD)
etoposide (ETP) with higher doses of recombinant
human (rh) granulocyte colony-stimulating
factor (G-CSF) is useful for peripheral
blood stem cell (PBSC) mobilization. 1-3 We
report the efficacy of HD-ETP with low-dose
rhG-CSF for PBSC mobilization in patients
with non-Hodgkin’s lymphoma (NHL).
Sir,
Twenty-three newly diagnosed patients (16
men and 7 women) with NHL were included in
this study.Their median age was 51 years (range,
20-66). They were treated with 2 or 3 courses of
CHOP therapy as an induction therapy. Twelve
patients entered complete remission (CR), 10
patients partial remission (PR), and one patient
had no change. Patients were treated with ETP
500 mg/m 2 i.v. for 2 hour daily on days 1 to 3.
rhG-CSF (Kirin Brewery Co., Tokyo, Japan) was
administered by s.c. injection at a dose of 50
µg/m 2 on the second day after completion of
Haematologica vol. 85(10):October 2000